QM and QM/MM study on inhibition mechanism of polyphenolic compounds as non-classical inhibitors of α-human carbonic anhydrase (II)

Phenolic and polyphenolic compounds are distributed in plant tissues as a secondary metabolite which compromised multiple imperative physiological phenomena. Herein, inhibition mechanism of human carbonic anhydrase isoform II, hCAII, with seven phenolic including phenol, catechol, resorcinol, 4-methyl vanillic acid, trans-cinnamic acid ortho-coumaric has been investigated using quantum mechanical ONIOM calculations. B3LYP-D3/6–311++G** method employed to calculate the electronic structure energy different species through reaction path. The model system hCAVII used that includes core catalytic center, Zn2+, binds three histidine residues hydroxide ion or water molecule forming first coordination shell. Thr199 Glu106 were considered neighboring ones binding zinc. All thermodynamic functions path evaluated phases. calculated results indicate all inhibitors do not directly interact zinc CA active presence aromatic moieties was associated more effective inhibition. In addition, implicit explicit solvent effect for QM (QM/MM)